William Leonard Scott

Solid-phase synthesis of unnatural amino acids using unactivated alkyl halides

Abstract Conditions were developed for the efficient alkylation of the resin-bound benzophenone imine of glycine with a variety of unreactive alkyl halides. Alkylations were accomplished at room temperature in NMP using the phosphazene-type base, BEMP.

Tandem UPS: Sequential mono- and dialkylation of resin-bound glycine via automated synthesis

Abstract A method has been developed for the synthesis of racemic α,α-disubstituted amino acids by a tandem alkylation process (“Tandem UPS”) on solid-support. Consecutive alkylations of Wang resin-bound benzophenone imines of glycine afforded unnatural, disubstituted amino acid derivatives. Automated chemical synthesis was used to efficiently optimize conditions for both formation and hydrolysis of resin-bound disubstituted benzophenone imines and to generate a matrix of disubstituted amino acid derivatives.

Synthesis of reagents for the one step incorporation of hydrazide functionality onto the lysine residues of proteins, and their use as linkers for carbonyl containing molecules

Two new reagents, 1 and 2, were prepared for the one step incorporation of hydrazide functionality onto the lysine residues of proteins. Their utility as linking reagents was demonstrated by their use in the coupling of two model aldehydes, and the anticancer agent doxorubicin, to a monoclonal antibody.